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Peginterferon and ribavirin in patients with HCV cirrhosis after liver transplantation.

The objective of the study was to assess the efficacy of antiviral therapy in patients with hepatitis C virus (HCV) recurrence after liver transplantation (OLT). We included 30 patients of mean age 56 years, who experienced HCV recurrence after OLT. Mean time from OLT to the beginning of therapy was 57 months (median: 43 months). All of them were on monotherapy: tacrolimus (n = 21), cyclosporine (n = 6), and mycophenolate mofetil (n = 3). Fourteen had previously been diagnosed with allograft HCV cirrhosis. Patients were treated with peginterferon alpha 2b (1.5 mug/kg/weekly SC) and ribavirin (10.6 mg/kg/d) for 48 (genotypes 1, 4) or 24 weeks (genotypes 2, 3). After a mean follow-up of 20 months, two patients had died due to biliary sepsis (while on therapy) and acute myocardial infarction (7 months after the end of therapy). End of treatment virological response was achieved in 19 patients (63.3%) and sustained virological response (SUR) in 14 (46.7%). Comparing cirrhotic and noncirrhotic patients, SVR was achieved in seven patients in both groups (50% vs 43.8%; P = .732). Every patient had some adverse event; in 11 patients (36.7%) it was withdrawn (seven cirrhotic and four noncirrhotic; P < .05), and in 12 the starting dose was decreased (40%). There were neither rejection episodes nor cirrhotic complications during therapy, but infections were more common in cirrhotic patients (57% vs 25%; P < .05). In HCV cirrhotic transplanted patients the sustained virological response to combined antiviral therapy was similar to that in noncirrhotic patients, but severe adverse events including infections were much more common.

Effectiveness of pegylated interferon and ribavirin in patients with liver HCV cirrhosis.

Clearance of HCV before transplantation could avoid recurrence of hepatitis C in the liver allograft, thereby improving graft and patient survival. We report our experience with combined therapy for patients with HCV cirrhosis, including 12 patients with biopsy-proven liver cirrhosis (n = 7) or previous cirrhotic complications (n = 5). The Child-Pugh score was A in eight patients and B in four. Two patients had hepatocellular carcinoma. Genotype distribution was 1a (n = 2), 1b (n = 8) or 3 (n = 1). Patients received peginterferon alpha2b (1.5 microg/kg once weekly) and ribavirin (10.6 g/kg per day) for 48 weeks (genotype 1) or 24 weeks (genotype 3). Twenty-one months after beginning therapy all the patients remained alive; three have undergone liver transplantation. In one patient treatment was discontinued after 2 months due to cachexia. End-of-treatment virologic response was achieved in five patients (41.7%) and sustained virologic response in three patients (25%). Patients who cleared the virus had negative PCR 4 weeks after beginning therapy. All patients had adverse events. The most common clinical events were asthenia, weight loss, fever, and anorexia. Infectious complications resolved in three patients (25%). Hematologic events were common. Seven of 11 patients (63.6%) who completed therapy required dose reduction. We conclude that therapy with peginterferon and ribavirin in patients with HCV cirrhosis has a similar effectiveness to previous treatments. A virologic response 1 month after the beginning of therapy could be a main predictor of a sustained response.

Efficacy of hepatocellular carcinoma locoregional therapies on patients waiting for liver transplantation.

The aim of this study was to evaluate the efficacy of different locoregional therapies in patients with HCC on the waiting list for liver transplantation. From October 2001 to July 2003, 13 patients, all men, with HCC diagnosed by cytology, were transplanted at our center. Locoregional therapies were percutaneous ethanol injection (PEI), transcatheter hepatic arterial chemoembolization (TACE), and radiofrequency microwave ablation (RFA). PEI was employed in seven patients, TACE in five (one of them associated with PEI) and RFA in one. Efficacy was evaluated by determining the percentage of tumoral necrosis in the liver explant. Five tumors were T4, four T3, three T2, and one T1. Ten were well differentiated, two moderately differentiated, and one undifferentiated. One patient died due to primary graft malfunction. After a median posttransplant follow-up of 15 months, 12 patients are alive with no sign of tumor recurrence. Most patients with solitary nodules <4 cm who received PEI had 90% to 100% tumor necrosis. Larger tumors had 25% to 30% necrosis. TACE was employed in six patients with large and/or multiple tumors, obtaining 20% to 50% tumor necrosis. RFA was employed in one case obtaining 85% necrosis (tumor of 4 cm). No serious complications occurred with any technique. According to our experience, PEI and RFA are effective locoregional therapies to treat hepatocellular carcinomas of <4 cm in patients on the waiting list. For larger tumors, their association with other techniques, such as TACE, seems adequate.

Prevalence of hepatitis C virus genotypes in a Spanish liver transplant unit.

INTRODUCTION: Among the at least six major identified genotypes of HCV, genotype 1b, the one associated with a poorer prognosis, is the most prevalent in Spain. We aimed to compare the distribution of hepatitis C virus genotypes in our liver transplant unit with that of the other HCV patients at our institution (n = 413) in order to assess whether genotype 1b is more prevalent among patients with more severe liver disease. PATIENTS AND METHODS: One hundred eight patients of mean age 56 years included 81 (75%) OLT recipients and 27 (25%) with HCV cirrhosis. Determination of HCV genotypes was made with the Inno-LiPA HCV III. RESULTS: The overall distribution of genotypes was: 1b, 93 patients (86.1%); 1a; eight patients (7.4%); 3, four patients (3.7%); 4; two patients (1.9%), and 2; one patient (0.9%). The distribution was similar among patients with cirrhosis and OLT. Genotype 1b patients were older. Eleven (78.6%) of 14 patients with hepatocellular carcinoma had genotype 1b. In the control group the distribution was: 1b, 287 patients (69.5%); 1a, 54 patients (12.1%); 3, 41 patients (9.9%); 4, 20 patients (4.8%), and genotype 2, 11 patients (2.7%). This differences in the distribution of genotypes between our population and the control group was statistically significant (P < .001). CONCLUSIONS: Genotype 1b, the most prevalent genotype in our liver transplant unit, included older patients in whom hepatocellular carcinoma was common, perhaps due to their higher prevalence of cirrhosis.

Adefovir dipivoxil therapy in liver transplant recipients with lamivudine-resistant hepatitis B virus.

Hepatitis B virus (HBV) infection is the leading cause of cirrhosis worldwide. One effective strategy to prevent recurrence or transmission of HBV infection after liver transplantation exists is prescription of Lamivudine, although it is associated with high resistance rates. Adefovir dipivoxil (AD) is a nucleotide analogue of adenosine that has achieved significant results in virologic, biochemical, and clinical parameters in lamivudine-resistant HBV-infected patients. Between 1990 and 2003 7 adult recipients of orthotopic liver transplants who experienced lamivudine-resistant HBV infection (pretransplantation or posttransplantation) were enrolled in a prospective study to administer AD for 48 weeks. At baseline they showed serum HBV DNA between 2.2 x 10(6) and 1.1 x 10(8) copies/mL. After 48 weeks of AD treatment, the median time-weighted average change in serum HBV DNA (log 10 copies/mL) was -3.19 (SD, 1.65). In 3 patients with HBV, DNA was undetectable (<400 copies/mL) at the end of the follow-up. HBe antigen seroconversion was observed in 1 patient. No significant adverse effects were recorded, except for renal functional impairment in 1 patient who had previous renal insufficiency. In our study, adefovir was an effective drug to suppression HBV replication in liver transplant recipients with lamivudine-resistant HBV. Excluding renal function abnormalities, tolerance of the drug was excellent. None of the patients developed resistance to adefovir. Therapy with AD in liver transplant recipients is effective and safe, although renal function should be monitored closely.

[Pneumocystis carinii pneumonia in patients with a solid organ transplant: a report of 5 cases]. / Neumonía por Pneumocystis carinii en pacientes con trasplante de órgano sólido: presentación de cinco casos.

A report is made here of five patients who underwent solid organ transplantation, were not infected with the human immunodeficiency virus, and suffered Pneumocystis carinii pneumonia while receiving immunosuppressive drugs. The figure represents a prevalence of 0.43% among patients with solid organ transplantation at the Clínica Puerta de Hierro. Some features of this infection are reported in patients without AIDS, both transplanted patients and with other clinical conditions, the possible predisposing factors and the necessity to keep a high suspect index when individuals treated with immunosuppressive drugs present with respiratory symptoms. Likewise, a suggestion is made to consider the use of chemoprophylaxis with cotrimoxazole in these cases.